脑缺血后周细胞及相关血管生成信号通路的研究进展

doi:10.3969/j.issn.1006-9771.2019.00.002

《中国康复理论与实践》 ›› 2019, Vol. 25 ›› Issue (5): 534-539.doi: 10.3969/j.issn.1006-9771.2019.00.002

脑缺血后周细胞及相关血管生成信号通路的研究进展

张荻¹, 徐鸣曙², 张英杰², 程爱芳¹, 管华宗¹

1.上海中医药大学，上海市 200120
2.上海市针灸经络研究所，上海市 200030

收稿日期:2018-08-30 修回日期:2018-10-19 出版日期:2019-05-25 发布日期:2019-05-29
通讯作者: 徐鸣曙(1978-)，男，汉族，河北人，博士，副研究员，主要研究方向：针灸治疗神经系统疾病。E-mail： mingshuxu@163.com
作者简介:张荻(1992-)，女，汉族，浙江嘉兴市人，硕士研究生，主要研究方向：针灸治疗神经系统疾病。
基金资助:
1.上海市科学技术委员会科研计划项目(No. 17ZR1427500)；2.上海市卫生和计划生育委员会科研课题计划项目(No. 201640128)

Advance in Pericytes and Related Angiogenic Signaling Pathways after Cerebral Ischemia (review)

ZHANG Di¹, XU Ming-shu², ZHANG Ying-jie², CHENG Ai-fang¹, GUAN Hua-zong¹

1.Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
2.Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China

Received:2018-08-30 Revised:2018-10-19 Published:2019-05-25 Online:2019-05-29
Contact: XU Ming-shu, E-mail: mingshuxu@163.com
Supported by:
Shanghai Committee of Science and Technology Research Plan (No. 17ZR1427500) and Shanghai Municipal Commission of Health and Family Planning Research Plan (No. 201640128)

摘要/Abstract

摘要： 周细胞与内皮细胞、星形胶质细胞以及胞外间隙共同构成血脑屏障(BBB)，周细胞与内皮细胞通过各种机制通路参与多种BBB的功能调节，共同维持神经血管单元(NVU)的稳定。NVU的损伤与修复涉及诸多分子水平的信号传递。血管生成主要是内皮细胞的发生成熟和周细胞的支持黏附过程。本文主要就目前NVU缺血损伤后周细胞与内皮细胞相关的血管生成信号通路研究进行综述。

关键词: 脑缺血, 周细胞, 内皮细胞, 血管生成, 神经血管单元

Abstract: Pericytes, endothelial cells (EC), astrocytes and extracellular space together constitute the blood-brain barrier. Pericytes and EC participate in the various regulations of blood-brain barriers through many mechanisms to maintain the stability of neurovascular units (NVU). The injury and repair of NVU involve a lot of signal transduction at molecular levels, and angiogenesis is primarily about the generation and maturation of EC and the supporting adhesion process of pericytes. This article briefly reviewed EC-related angiogenesis signaling pathways in pericytes after NVU ischemic injury.

Key words: cerebral ischemia, pericytes, endothelial cell, angiogenesis, neurovascular unit

中图分类号:

R743.3

张荻, 徐鸣曙, 张英杰, 程爱芳, 管华宗. 脑缺血后周细胞及相关血管生成信号通路的研究进展[J]. 《中国康复理论与实践》, 2019, 25(5): 534-539.

ZHANG Di, XU Ming-shu, ZHANG Ying-jie, CHENG Ai-fang, GUAN Hua-zong. Advance in Pericytes and Related Angiogenic Signaling Pathways after Cerebral Ischemia (review)[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2019, 25(5): 534-539.

参考文献

1 HoffmannC J, HarmsU, RexA, et al. Vascular signal transducer and activator of transcription-3 promotes angiogenesis and neuroplasticity long-term after stroke [J]. Circulation, 2015, 131(20): 1772-1782.
2 HermannD M, AnilZ, BrittaK, et al. Sustained neurological recovery induced by resveratrol is associated with angioneurogenesis rather than neuroprotection after focal cerebral ischemia [J]. Neurobiol Dis, 2015, 83: 16-25.
3 Dore-DuffyP. Pericytes: pluripotent cells of the blood brain barrier [J]. Curr Pharm Des, 2008, 14(16): 1581-1593.
4 KrupinskiJ, KaluzaJ, KumarP, et al. Prognostic value of blood vessel density in ischaemic stroke [J]. Lancet, 1993, 342(8873): 742.
5 OtrockZ K, MahfouzR A, MakaremJ A, et al. Understanding the biology of angiogenesis: review of the most important molecular mechanisms [J]. Blood Cells Mol Dis, 2007, 39(2): 212-220.
6 QuittetM S, TouzaniO, SindjiL, et al. Effects of mesenchymal stem cell therapy, in association with pharmacologically active microcarriers releasing VEGF, in an ischaemic stroke model in the rat [J]. Acta Biomater, 2015, 15: 77-88.
7 YangX, ZhuH, GeY, et al. Melittin enhances radiosensitivity of hypoxic head and neck squamous cell carcinoma by suppressing HIF-1α [J]. Tumour Biol, 2014, 35(10): 10443-10448.
8 ZhangX, LassilaM, CooperM E, et al. Retinal expression of vascular endothelial growth factor is mediated by angiotensin type 1 and type 2 receptors [J]. Hypertension, 2004, 43(2): 276.
9 JainR K. Molecular regulation of vessel maturation [J]. Nat Med, 2003, 9(6): 685-693.
10 CaporaliA, MartelloA, MiscianinovV, et al. Contribution of pericyte paracrine regulation of the endothelium to angiogenesis [J]. Pharmacol Ther, 2016, 171: 56.
11 AugustinH G, GouY K, ThurstonG, et al. Control of vascular morphogenesis and homeostasis through the angiopoietin–Tie system [J]. Nat Rev Mol Cell Biol, 2009, 10(3): 165-177.
12 HolgerG, MatthewG, MarcusF, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia [J]. J Cell Biol, 2003, 161(6): 1163-1177.
13 IsogaiS, LawsonN D, TorrealdayS, et al. Angiogenic network formation in the developing vertebrate trunk [J]. Development, 2003, 130(21): 5281-5290.
14 MargaritescuO, PiriciD, MargaritescuC. VEGF expression in human brain tissue after acute ischemic stroke [J]. Rom J Morphol Embryol, 2011, 52(4): 1283-1292.
15 LeeS C, LeeK Y, KimY J, et al. Serum VEGF levels in acute ischaemic strokes are correlated with long-term prognosis [J]. Eur J Neurol, 2010, 17(1): 45-51.
16 GreenbergD A, JinK. Vascular endothelial growth factors (VEGFs) and stroke [J]. Cell Mol Life Sci, 2013, 70(10): 1753.
17 ZechariahA, ElaliA, DoeppnerT R, et al. Vascular endothelial growth factor promotes pericyte coverage of brain capillaries, improves cerebral blood flow during subsequent focal cerebral ischemia, and preserves the metabolic penumbra [J]. Stroke, 2013, 44(6): 1690-1697.
18 ShenS W, DuanC L, ChenX H, et al. Neurogenic effect of VEGF is related to increase of astrocytes transdifferentiation into new mature neurons in rat brains after stroke [J]. Neuropharmacology, 2016, 108: 451-461.
19 RibattiD, NicoB, CrivellatoE. The role of pericytes in angiogenesis [J]. Int J Dev Biol, 2011, 55(3): 261-268.
20 CristofaroB, ShiY, FariaM, et al. Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models [J]. Development, 2013, 140(8): 1720-1729.
21 GaleN W, DominguezM G, NogueraI, et al. Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development [J]. Proc Natl Acad Sci U S A, 2004, 101(45): 15949-15954.
22 ChappellJ C, MouillesseauxK P, BautchV L. Flt-1 (vascular endothelial growth factor receptor-1) is essential for the vascular endothelial growth factor-Notch feedback loop during angiogenesis [J]. Arterioscler Thromb Vasc Biol, 2013, 33(8): 1952-1959.
23 RanQ, YuY, FuX, et al. Activation of the Notch signaling pathway promotes neurovascular repair after traumatic brain injury [J]. Neural Regener Res, 2015, 10(8): 1258-1264.
24 YamamotoY, CraggsL, BaumannM, et al. Review: molecular genetics and pathology of hereditary small vessel diseases of the brain [J]. Neuropathol Appl Neurobiol, 2011, 37(1): 94-113.
25 王拯,张莛蔚,韩向龙. Notch信号通路调控下的血管形成[J]. 中国组织工程研究, 2015, 19(46): 7498-7503.
26 LiuJ, WangY, AkamatsuY, et al. Vascular remodeling after ischemic stroke: mechanisms and therapeutic potentials [J]. Prog Neurobiol, 2014, 115(2): 138-156.
27 赵雅宁,刘文倩,牛静,等. 参芎化瘀胶囊通过VEGF/Notch1信号通路改善大鼠缺血性脑卒中损伤[J]. 西安交通大学学报(医学版), 2014, 35(06): 843-847.
28 董丽,孔令蕊,王恬. Notch信号通路对免疫细胞的调节作用[J]. 中国生物化学与分子生物学报, 2013, 29(12): 1106-1112.
29 GuA, ShivelyJ E. Angiopoietins-1 and -2 play opposing roles in endothelial sprouting of embryoid bodies in 3D culture and their receptor Tie-2 associates with the cell-cell adhesion molecule PECAM1 [J]. Exp Cell Res, 2011, 317(15): 2171.
30 MarronM B, SinghH, TahirT A, et al. Regulated proteolytic processing of Tie1 modulates ligand responsiveness of the receptor-tyrosine kinase Tie2 [J]. J Biol Chem, 2007, 282(42): 30509-30517.
31 SuH, TakagawaJ, HuangY, et al. Additive effect of AAV-mediated angiopoietin-1 and VEGF expression on the therapy of infarcted heart [J]. Int J Cardiol, 2009, 133(2): 191-197.
32 ArmulikA, AbramssonA, BetsholtzC. Endothelial/pericyte interactions [J]. Circ Res, 2005, 97(6): 512-523.
33 FagianiE, LorentzP, KopfsteinL, et al. Angiopoietin-1 and -2 exert antagonistic functions in tumor angiogenesis, yet both induce lymph angiogenesis [J]. Cancer Res, 2011, 71(17): 5717-5727.
34 HuangH, BhatA, WoodnuttG, et al. Targeting the ANGPT-TIE2 pathway in malignancy [J]. Nat Rev Cancer, 2010, 10(8): 575.
35 ZhengQ, ZhuD, BaiY, et al. Exercise improves recovery after ischemic brain injury by inducing the expression of angiopoietin-1 and Tie-2 in rats [J]. Tohoku J Exp Med, 2010, 224(3): 221-228.
36 CiprianiP, MarrelliA, BenedettoP D, et al. Scleroderma mesenchymal stem cells display a different phenotype from healthy controls: implications for regenerative medicine [J]. Angiogenesis, 2013, 16(3): 595-607.
37 ArmulikA, MäeM, BetsholtzC. Pericytes and the blood-brain barrier: recent advances and implications for the delivery of CNS therapy [J]. Ther Delivery, 2011, 2(4): 419.
38 WilkersonB A, ArgravesK M. The role of sphingosine-1-phosphate in endothelial barrier function [J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2014, 1841(10): 1403-1412.
39 MercadopimentelM E, RunyanR B. Multiple transforming growth factor-beta isoforms and receptors function during epithelial-mesenchymal cell transformation in the embryonic heart [J]. Cells Tissues Organs, 2007, 185(1-3): 146-156.
40 SinhaS, HoofnagleM H, KingstonP A, et al. Transforming growth factor-beta 1 signaling contributes to development of smooth muscle cells from embryonic stem cells [J]. Am J Physiol, 2004, 287: 1560-1568.
41 GreenbergJ I, Shields ProiaR L, HlaT. Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy [J]. J Clin Invest, 2015, 125(4): 1379.
42 GreenbergJ I, ShieldsD J, BarillasS G, et al. A role for VEGF as a negative regulator of pericyte function and vessel maturation [J]. Nature, 2008, 456: 809-813.
43 CarmelietP. Angiogenesis in life, disease and medicine [J]. Nature, 2005, 438: 932-936.
44 LimaS, MilstienS, SpiegelS. Sphingosine and sphingosine kinase 1 involvement in endocytic membrane trafficking [J]. J Biol Chem, 2017, 292(8): 3074-3088.
45 LinJ J, ChangT, CaiW K, et al. Post-injury administration of allicin attenuates ischemic brain injury through sphingosine kinase 2: In vivo and in vitro studies [J]. Neurochem Int, 2015, 89: 92-100.
46 KruegerM, BechmannI. CNS pericytes: concepts, misconceptions, and a way out [J]. Glia, 2010, 58(1): 1-10.
47 臧妍妍,李卫红,张赛,等. TGF-β信号转导通路在缺血性脑损伤中的分子机制研究[J]. 云南中医学院学报, 2016, 39(4): 94-98.
48 孙伟,苏志强,宋丽,等. 大鼠局灶性脑缺血再灌注中1-磷酸鞘氨醇受体1的表达变化[J]. 中风与神经疾病杂志, 2011, 28(2): 108-110.
49 TanimotoT, JinZ G, BerkB C. Transactivation of VEGF receptor Flk-1/KDR is involved in sphingosine 1-phosphate-stimulated phosphorylation of Akt and eNOS [J]. J Biol Chem, 2002, 277(45): 42997-43001.
50 HlaT. Physiological and pathological actions of sphingosine 1-phosphate [J]. Semin Cell Dev Biol, 2004, 15(5): 513-520.
51 BazzaziH, PopelA S. Computational investigation of sphingosine kinase 1 (SphK1) and calcium dependent ERK1/2 activation downstream of VEGFR2 in endothelial cells [J]. PLoS Comput Biol, 2017, 13(2): e1005332.
52 LeeS W, MoskowitzM A, SimsJ R. Sonic hedgehog inversely regulates the expression of angiopoietin-1 and angiopoietin-2 in fibroblasts [J]. Int J Mol Med, 2007, 19(3): 445.
53 WalsheT E, ConnellP, CryanL, et al. Microvascular retinal endothelial and pericyte cell apoptosis in vitro: role of hedgehog and notch signaling [J]. Invest Ophthalmol Visual Sci, 2011, 52(7): 4472-4483.
54 SongN, HuangY, ShiH, et al. Overexpression of platelet-derived growth factor-BB increases tumor pericyte content via stromal-derived factor-1alpha/CXCR4 axis [J]. Cancer Res, 2009, 69(15): 6057-6064.
55 蒋福林,艾冬青,官秋玥. 周细胞概念及在血管形成信号转导通路研究中的进展[J]. 中国组织工程研究, 2015, 19(46): 7504-7508.
56 BethaniI, SkånlandS S, DikicI, et al. Spatial organization of transmembrane receptor signaling [J]. EMBO J, 2010, 29(16): 2677-2688.

[1]	康晓宇, 刘丽旭, 王文竹, 王云雷. 普拉克索联合左旋多巴对全脑缺血再灌注损伤大鼠认知能力及线粒体功能的影响[J]. 《中国康复理论与实践》, 2023, 29(5): 533-540.
[2]	缪培,张通,米海霞,张伟东. 不同线栓法复制局灶性脑缺血模型大鼠恢复期学习记忆能力的差异及其机制[J]. 《中国康复理论与实践》, 2022, 28(7): 789-796.
[3]	黄菲菲,王万松,董晓阳,冯珍. 高压氧修复缺血再灌注损伤大鼠血脑屏障的自噬机制[J]. 《中国康复理论与实践》, 2022, 28(4): 415-420.
[4]	周文美,陶陶,吴霜,王廷龙,杨正奕,张莹. 丰富环境对脑缺血再灌注损伤大鼠神经功能和缺血半暗带区葡萄糖代谢的影响[J]. 《中国康复理论与实践》, 2021, 27(5): 522-529.
[5]	杨赫,唐强,朱路文. 针康法对脑缺血小鼠神经功能及叉头转录因子3和维甲酸相关孤儿受体γt表达的影响[J]. 《中国康复理论与实践》, 2021, 27(12): 1437-1442.
[6]	彭志锋, 张义平, 张继红. 早期运动联合戊四氮对脑缺血再灌注大鼠神经功能的效果及其机制[J]. 《中国康复理论与实践》, 2021, 27(1): 27-30.
[7]	陈小平,王明洋,马登磊,龚诗立,张丽,李雅莉,李林,胡朝英,张兰. 痘苗病毒致炎兔皮提取物对脑缺血再灌注脑损伤大鼠凋亡和神经炎症的影响[J]. 《中国康复理论与实践》, 2020, 26(9): 1038-1044.
[8]	陶苗苗,徐鸣曙,张英杰,程爱芳,邓韵怡. 线粒体介导远端缺血后处理抗脑缺血再灌注损伤的机制研究进展[J]. 《中国康复理论与实践》, 2020, 26(9): 1061-1065.
[9]	王慧灵,冯晓东,李瑞青,兰晓燕,赵薇,张铭. 表面肌电图在环咽肌失弛缓患者吞咽障碍评定中的应用[J]. 《中国康复理论与实践》, 2020, 26(11): 1275-1279.
[10]	苏明珠,马跃文. Notch和Wnt通路对脑缺血后神经干细胞作用的研究进展[J]. 《中国康复理论与实践》, 2020, 26(1): 55-58.
[11]	秦文熠, 荣晓凤, 罗勇. 电针通过调节IκB激酶β表达抑制局灶性脑缺血再灌注大鼠脑内炎症损害的机制[J]. 《中国康复理论与实践》, 2019, 25(4): 407-415.
[12]	梁碧莹, 朱路文, 唐强, 叶涛, 李宏玉, 李保龙, 阮野. 运动预处理对大鼠脑缺血再灌注损伤后血脑屏障通透性的影响[J]. 《中国康复理论与实践》, 2019, 25(3): 302-306.
[13]	范加维, 杨拯, 王近吴, 范道贵, 蒋仕秋, 曾江华, 易红梅, 戴小珍, 刘海荣. 内皮祖细胞CXC趋化因子受体7对脑缺血再灌注后血管新生的作用[J]. 《中国康复理论与实践》, 2019, 25(11): 1283-1292.
[14]	田超, 玛娜璐璐, 袁梦晨, 王丽琴, 安娜, 张涵莱, 邢雁伟, 孙逸坤, 高永红. 清开灵对小胶质细胞缺氧活化诱导的脑微血管内皮细胞Toll样受体4、gp91^phox和闭锁小带蛋白-1表达的影响[J]. 《中国康复理论与实践》, 2019, 25(11): 1303-1308.
[15]	宁文华, 李礼, 郭扬, 张宝瑜, 王洋, 赵梦雄, 王舒. 电针预处理脑保护作用机制研究进展[J]. 《中国康复理论与实践》, 2019, 25(11): 1315-1319.

脑缺血后周细胞及相关血管生成信号通路的研究进展

Advance in Pericytes and Related Angiogenic Signaling Pathways after Cerebral Ischemia (review)

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

Metrics

本文评价

推荐阅读 0